This application is a proposal for the investigation of lung microvascular filtration by the direct micropuncture technique. Two general aims govern this proposal: first, to determine whether filtration varies longitudinally along the microvascular tree, second, to quantify hydraulic conductance and macromulecular flux across the single lung microvessel. A major new experiment concerns determination of transmicrovascular liquid flux in single lung microvessels. We will modify the split-drop technique to directly characterize filtration and sieving in single 30 Mum arterioles and venules to determine the effects of intravascular protein content, macromolecular change and mediators on microvascular liquid flux. We will continue to use the whole organ approach with which we will characterize filtration as a function of vascular pressure in extra-alveolar vessels of dog and sheep lungs. For the first time, we will make microvascular pressure measurements in the intact dog lung. In the excised dog lung, we will compare microvascular pressures measured by the micropuncture, the occlusion and the isogravimetric techniques. In addition, we plan to determine the effects of blood flow and of several mediators on the microvascular pressure profile. To characterize the pressure-flow profile of the subpleural microcirculation, each measurement of microvascular pressure will be accompanied by a measurement of microvascular blood velocity. With regard to interstitial liquid pressure, we will determine the arterio-venous distribution, and the effects of lung inflation. Using chemical analyses of nanoliter volumes of interstitial fluid directly sampled by micropuncture, we will explore interstitial liquid protein composition to compute interstitial protein osmotic pressure and to determine the profile of interstitial macromolecular sieving. Using our combined data we will estimate membrane coefficients which quantify microvascular flux of water and macromolecules. We will continue to develop a complex, multi-segmental model of liquid and solute exchange incorporating regional heterogeneities. The results of our investigations will elucidate fundamental mechanisms in the regional control of lung microvascular permeability and will promote our understanding of the fundamental processes of pulmonary edema.
| Hough, Rebecca F; Bhattacharya, Sunita; Bhattacharya, Jahar (2018) Crosstalk signaling between alveoli and capillaries. Pulm Circ 8:2045894018783735 |
| Hook, Jaime L; Islam, Mohammad N; Parker, Dane et al. (2018) Disruption of staphylococcal aggregation protects against lethal lung injury. J Clin Invest 128:1074-1086 |
| Sinha, Pratik; Islam, Mohammad N; Bhattacharya, Sunita et al. (2016) Intercellular mitochondrial transfer: bioenergetic crosstalk between cells. Curr Opin Genet Dev 38:97-101 |
| Bhattacharya, Jahar; Westphalen, Kristin (2016) Macrophage-epithelial interactions in pulmonary alveoli. Semin Immunopathol 38:461-9 |
| Looney, Mark R; Bhattacharya, Jahar (2014) Live imaging of the lung. Annu Rev Physiol 76:431-45 |
| Islam, Mohammad N; Gusarova, Galina A; Monma, Eiji et al. (2014) F-actin scaffold stabilizes lamellar bodies during surfactant secretion. Am J Physiol Lung Cell Mol Physiol 306:L50-7 |
| Huertas, Alice; Das, Shonit R; Emin, Memet et al. (2013) Erythrocytes induce proinflammatory endothelial activation in hypoxia. Am J Respir Cell Mol Biol 48:78-86 |
| Bhattacharya, Jahar; Matthay, Michael A (2013) Regulation and repair of the alveolar-capillary barrier in acute lung injury. Annu Rev Physiol 75:593-615 |
| Quadri, Sadiqa K; Sun, Li; Islam, Mohammad Naimul et al. (2012) Cadherin selectivity filter regulates endothelial sieving properties. Nat Commun 3:1099 |
| Quadri, Sadiqa K (2012) Cross talk between focal adhesion kinase and cadherins: role in regulating endothelial barrier function. Microvasc Res 83:3-11 |
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